Today, millions of Americans have had bariatric surgery, and given the magnitude of the obesity epidemic, it is anticipated that this number will continue to rise. Despite the numerous health benefits of these procedures, there is a growing concern with the development of alcohol problems after gastric bypass surgery. We believe that changes in alcohol pharmacokinetics and subjective responses to alcohol that occur as a result of the anatomical and physiological changes caused by upper gastrointestinal tract diversion might be an important mechanism responsible for the association between gastric bypass surgery and postoperative alcohol abuse. The current proposal will be the first study that will investigate the effects of gastric bypass surgery on subjective responses to alcohol and alcohol pharmacokinetic using validated methods and controlling for the important confounding effect of changes in body weight. Patients who will undergo gastric bypass surgery and a group of patients undergoing banding gastric surgery will be evaluated 3 times before and 3 times 9 m after surgery following identical procedures. Unlike after gastric bypass, the anatomy of the intestine/stomach is intact after gastric banding. Thus, gastric banding subjects will allow controlling for changes in alcohol metabolism and mood effects that could be caused by weight loss. Breath and blood samples will be taken before and at various times after a dose of alcohol (0.8 or 1.4 g/l of total body water) or non-alcoholic placebo control are consumed. Blood alcohol concentrations (BAC) will be determined by the gold standard technique of headspace gas chromatography and these concentrations will be compared with the BAC estimated from breath samples. Subjective ratings of alcohol effects will be measured by validated questionnaires extensively used in the field. The results from our study will lay the foundation for understanding the effect of gastric bypass and gastric banding procedures on alcohol kinetics and pharmacodynamics, which can help tailor counseling in patients undergoing these procedures and prevent alcohol misuse after surgery. PUBLIC HEALTH RELEVANCE: Although gastric bypass surgery provides one of the most successful long-term treatments for obesity and is associated with numerous health benefits, there is an increasing concern about the development of alcohol problems after this procedure. The results from our study will lay the foundation for understanding how gastric bypass surgery affects the way alcohol is processed by the body and the effects that alcohol has on patients after surgery. This evidence-base data will support patient counseling and may help in the prevention of alcohol misuse after gastric bypass surgery.